Overview

• The study published in June 2025 identifies HKU5 bat coronaviruses as one small mutation away from efficient human ACE2 binding.
• Researchers demonstrated using AlphaFold3 that subtle changes in the spike protein could enable cross-species transmission.
• A lineage of HKU5 has already shown the ability to bind human ACE2 and infect minks, indicating natural spillover potential.
• Structural analyses including cryo-electron microscopy indicate key spike segments remain closed but may open with mutations.
• Experts warn that unregulated wildlife trade in China could elevate the risk of HKU5 spillover events, underscoring the need for continued surveillance.